Drug interactions

Drug–drug interactions (DDIs) arise when the effects of one drug are altered by the co-administration of another. The clinical response depends on many factors, including individual patient characteristics such as age, co-morbidities and pharmacogenetics. The number of potential DDIs is extensive, but the incidence in published studies implies that many of these are not clinically relevant. Interactions are classified as pharmacokinetics-related, where drug absorption, distribution, metabolism or excretion is affected, or pharmacodynamics-related, when drugs with similar pharmacological actions are co-prescribed. The mechanism underlying drug interactions are now better understood, notably those involving the family of cytochrome P450 isoenzymes, as well as those related to P-glycoprotein and organic anion transporter polypeptides, which act as drug transporters in the liver and kidneys. These molecules exhibit genetic polymorphisms that influence the likelihood of clinically relevant DDIs following drug co-administration. With an ageing population, an increasing number of new drugs and more polypharmacy, increasing efforts are needed to avoid DDIs. Although computerized programs can reduce the number of DDIs, a risk–benefit evaluation by the prescribing physician is also required. This article outlines the main mechanisms involved in clinically relevant DDIs.